The proposed experiments aim at an evaluation of embryotoxic interactions between polychlorinated biphenyls (PCBs) as the primary chemical insult to embryonal tissues followed by a well established teratogen as a secondary insult. PCBs are notorious as nonbiodegradable chemical pollutants. A large section of the population in this country has body burdens of these chemicals. PCBs are embryotoxic in a large variety of mammalian species including man. Two model teratogens, cyclophosphamide (CPA) and 5-fluorodeoxyuridine (FUdR), were chosen. Either one will be administered to 11 day pregnant mice which are a) control mice, or b) acutely PCBs exposed animals (from day 6 of gestation on), or c) chronically exposed mice (3 months prior to breeding). The doses to be administered are a) at threshold for teratogenesis, or b) highly teratogenic in positive control mice. On day 18 all fetuses will be examined for malformations. A major concept to be examined is modulation of teratogenesis by PCBs. This could be in the sense of potentiation of attenuation of teratogenesis. The in vivo experiments will be correlated with the in vitro organ culture, in which forelimb buds from 11 day old mouse embryos with or without previous exposure to PCBs in utero will be treated with precisely defined concentrations of the model teratogens to examine whether or not PCBs have altered the embryonal tissue response to a secondary embryotoxin. The experimental protocol includes a quantitative assessment by gas chromatography of the placental transfer and accumulation in mouse embryos of various dietary intake levels of PCBs. Maternal liver enzyme activities coupled to the cytochromes P450 and P448 will be measured as biochemical indicators of enzyme induction. Furthermore the effects of PCBs on the pharmacokinetics, placental transfer and binding of 14C-CPA and 3H-FUdR to embryonal macromolecules will be measured.